While attending the University of Miami,[7] Landis wrote numerous shorts which were produced by students in the school's film program. Upon leaving the university, Landis went on a "spec-selling streak", having three of his pitches optioned within six months.[8] First, Landis sold Chronicle to producer John Davis and 20th Century Fox's Davis Entertainment. The Chronicle script was previously included on the Black List, an annual compendium of the year's best unproduced screenplays.[9] A documentary-style movie about three Seattle teenagers that develop superpowers after encountering a strange substance in the woods, Chronicle was directed by Josh Trank,[10] and takes a different approach to handling superpowered characters.[11]

20th Century Fox's Davis Entertainment hired Landis in May 2011 to script a reimagining of the German fairy tale of the Pied Piper. The project has been characterized as a "fantasy thriller" and is being overseen by Steve Asbell.[15] Davis and Fox again opted to team with Landis for a film based on Mary Shelley's Frankenstein.[16] The adaptation is rumored to be a retelling of the story from Igor's point of view.[17] The character breakdowns from Landis' script also suggest that the tale has been transported to a circus setting.[18] In September 2012, it was announced that Sherlock and Push director Paul McGuigan will be the movie's director.[19]

In January 2012, Variety reported that Disney picked up a pitch Landis made for a space adventure focusing on a brother and sister. The film is set to be produced by Wedding Crashers producer Andrew Panay.[20] According to Landis' Twitter account, he is also working on a project entitled Villains.[21]

It was revealed in April 2012 that Landis would produce his first movie, an "edgy family adventure" named Woogles, along with Bazelevs producers Michele Wolkoff and Timur Bekmambetov. The project will be written by Nick Antosca and Ned Vizzini and is based on a script Landis wrote in college.[22] During an interview at the Middle East Film and Comic Con, Landis also revealed he was planning to direct a screenplay he wrote entitled Me, Him, Her.[13]

In September 2012, The Hollywood Reporter reported that Landis created a TV series for Fox and would executive produce it with Homeland producer Howard Gordon. The series, entitled Vigilant, centers on a young woman who creates a fictional vigilante persona to stop crime and combat a brutally coercive police department and its corrupt internal affairs department. Landis will also write the pilot script.[23] Though the initial report described the show as a "superhero police drama," Landis said on his Twitter that it is not a superhero show and "has more in common with The Wire than Smallville."[24]

Chronicle was released on February 3, 2012. It received wide acclaim and currently holds a "Fresh" rating of 85% on Rotten Tomatoes, which said the film "transcends its gimmicks with a smart script, fast-paced direction, and engaging performances from its young, talented cast".[27]Chicago Sun-Times film critic Roger Ebert praised the movie, saying, "sometimes a movie arrives out of the blue that announces the arrival of considerable new talents", and singling out Landis' dialogue as adding a natural authenticity to the proceedings.[28] The film opened in 2,907 theaters and exceeded expectations by grossing $22,000,000 to win the weekend box office.[29] As of March 12 it has grossed over $62,000,000.[30] It was announced in early March that Landis would pen a sequel for Fox.[31]

On October 10, 2012 it was revealed that Fox was unhappy with Landis' draft for Chronicle 2.[34] On July 18, 2013, Landis confirmed he was no longer attached to Chronicle 2, saying he was "off Chronicle 2 for months now". In November 2014, Landis revealed in a reddit post that he was working on a "WWE-centric sequel" to The Death and Return of Superman.[35] The film, Wrestling Isn't Wrestling, was released online on March 16, 2015.[36]

In February 2015, Landis directed Ariana Grande's music video One Last Time.

Landis is an avid fan of professional wrestling. In 2012, he appeared on a podcast by Esther Povitsky alongside WWE wrestler Dolph Ziggler;[37] during the podcast, Povitsky continually attempted to decry professional wrestling, causing a frustrated Landis to fervently defend it in a lengthy speech.[38] He also recently directed, wrote, and narrated Wrestling Isn't Wrestling, a short film chronicling the career of wrestler Triple H, done in the style of his short film The Death and Return of Superman.